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Staff Spotlight: Somasish Dastidar, PhD

Wednesday, February 21, 2018

Somashish Dastidar, PhD, was five years old when a cousin, a biologist, got him interested in the natural world--first by teaching him the scientific names for animals he saw, and then by introducing him to the world of microbes. Now, as a member of our Center for Neurodegeneration and Neurotherapeutics, Dastidar is studying the origins of ALS4 and how this disease subtype compares to the more common forms of ALS. In this week’s Staff Spotlight, Dastidar talks to us about this journey, how North Carolina compares to his former home of San Diego, and painting in oils and reading detective novels in two languages in his spare time.

What are your responsibilities within the Neurology Department? What does your average work day look like?
I am a senior research associate here at Duke. I am involved with three major projects and their affiliated sub-projects. I am currently studying the relation of MAP4K3, a protein involved in mTOR pathway, to Transcription Factor EB (TFEB) involved in lysosomal biogenesis and autophagy; Role of L389S and R2136H mutations in Senataxin which cause Ayotropic Lateral Sclerosis 4 along the relevance of Senataxin in Amyotropic Lateral Sclerosis caused due to hexanucleotide repeats in C9ORF72.

Finally I have Al’s tremendous support to investigate if reduced protein translation in postmitotic neurons can provide better protein quality control during stress encountered during neurodegenerative conditions. This project is directed towards my independence as I prepare to apply for faculty position in India and elsewhere.

I consider myself very lucky to work with eight different mouse lines (transgenic/Knock In) designed to address various questions pertaining to the three projects I am engaged with. I manage these mice with help from my undergraduates and mice technicians. Running experiments on bench, confocal imaging, designing experiments, analyzing results, working on manuscript, discussion with my colleagues in the lab and outside to design experiments or transfer of technology and grantsmanship, sharing my expertise with fellow labmates for their scientific projects comprise an average day in the lab.

I am very passionate about training undergraduate and graduate students who can handle projects with minimal supervision and contribute significantly towards common scientific questions. Indeed, I am highly indebted to my undergraduate/graduate research assistants for this contribution towards my research goals.

Dastidar and his undergraduate students from the University of California, San Diego, celebrate a colleague's thesis defense.

How did you first get interested in micro and molecular biology? What do you enjoy most about your work?
I grew up in a joint family among many “cousin brothers and sisters” back in India. One of my cousin brothers was a biologist. It was due to him that I was introduced to the fascinating world around us and the fact that each organism has a scientific name. I was probably 5-6 years old when he started my schooling in biology (particularly zoology and botany). I was able to identify and name many species at an early age all because of his persistence. He would be very fascinated himself about nature and take me around in his bicycle introducing more new species as I grew older. He also convinced me that my scientific name was Macaca mulatta [a species of Rhesus monkey] , if anybody asked! But as I was growing older he spoke about another world of organisms that we cannot see with our naked eyes, the world of microbes.

This curiosity culminated into a bachelor's degree in microbiology from one of the best universities in India and a Masters in biotechnology, with a thesis work in microbiology. During my Masters, I got introduced to molecular biology and got very interested in it. Later on I pursued a PhD in molecular and cell biology in the Department of Cell and Molecular biology, UT Dallas. Though I selected the department for the good microbiology labs in it, I ended up in the lab of Dr. Santosh D’Mello, a neurobiologist. He studied neurodegeneration and I continue to do so in Al’s lab using molecular biology as a tool.

I have always been fascinated to know about the behavior of proteins/genes and their biology that is unexplored. I have been very lucky in my predoctoral and postdoctoral studies where I get to study in areas where there is a lot to learn and explore the unknown. I cannot say whether it is a boon or bane that I work in areas which are very pristine and organic and may be deemed low risk projects as there are very few colleagues working in it. At core I am a biologist with an allegiance towards basic research. I cater to it most respectfully and I get excited at the thought that whatever little contribution I can make will lay the basis for hopefully translational research. But in parallel, I find translational research equally appealing and one of my projects caters to that curiosity of mine. Every day I learn new things and face new challenges and sometimes big disappointments. The whole package is a hobby enveloped in a job.

You recently submitted a manuscript for publication. What were the main findings of that research? What implications does that work have for patient care?
We are currently working on the revision of that manuscript. This work is to understand the etiology of Amyotropic Lateral Sclerosis 4 caused by the mutation of Senataxin. We designed two mice models one a Knock-in with a L389S mutation in Senataxin and the other a transgenic mice with R2136H mutation in Senataxin. We have extensively studied these mice to find that these mice have abnormalities in their lower and upper motor neurons, defects in proteins transport across the nuclear membrane.

But most importantly it shares some overlapping pathology with the canonical ALS. These mice models mirror the human pathophysiology quiet remarkably and thus is an important resource for us to study ALS4 in a 3D paradigm. We are quite confident that as we delve deeper into these mice we will unravel more basic biology about the Senataxin mutations that causes the disease. This will helps us to identify drugable targets in some time to come.

Additionally, I have been working on the effects of reduced protein translation in normal neuronal health and in neurodegenerative conditions. We find that reduced protein translation leads to protection of primary neurons from drugs that mimic Parkinsonism. With the support of my undergraduates I was able to decipher the putative pathways through which reduced protein translation offers neuroprotection. This work is based primary in vitro but in future I would like to examine similar questions in an in vivo setting. This work is very translational and hopefully it might lead to deciphering more avenues towards better management of Parkinson’s. I am very grateful to Dr. La Spada for supporting me on this project which I am engaged with to carve a niche for myself towards my independence.

How has our understanding of these areas changed since you earned your PhD? What advances do you see coming over the next decade?
Our recent findings though our own work and collaborations with Dr. Paul Taylor’s lab and Dr. Uday Panday’s lab is hinting at Senataxin to be a modulator/ important protein whose function is disrupted in canonical ALS. We just set up a collaboration with Dr. Jack Keene’s laboratory here at Duke and making an effort to have an in depth analysis towards the biology of Senataxin that is affected in ALS pathogenesis. Second, the role of reduced protein translation towards better proteostasis in postmitotic neurons is very organic and a whole new perspective towards translational biology.

I am a great fan of the pioneers in the field who are constantly striving to develop better models (invertebrate and vertebrate) to study neurodegenerative diseases and with CRISPR/Cas9 involvement and out of the box strategy towards translational goals such as what we strive for in the La Spada laboratory, I see more significant strides in that direction in the next decade.

You came to Duke from the University of California-San Diego as part of the team of Al La Spada, MD, PhD late last year. What’s the biggest difference you experienced between UCSD and Duke so far?
Honestly it is too premature to compare the two institutes. Scientifically I feel that both the places are top notch. I am a big fan of the supporting staff here. I am thankful and grateful to the faculty, staff and our Departmental Chair Dr. O’Brien at the Neurology department, the Director for the center of Neurodegeneration and Neurotherapeutics Dr. Al La Spada, who went out of their way to make my transition and integration to the department very smooth.

My collaboration with the Keene lab, for a vital experimentation on identifying shared RNA targets between Senataxin and toxic dipeptides which arises due to hexanucleotide repeats in C9ORF72 happened in no time and the work is already set into motion by a great friend in the Keen lab, Dr. Matt Friedersdorf. I am so grateful to them and equally to Al for his unwavering support towards this project which I started in UCSD. I feel the weather and health insurance in UCSD was more appealing to me. The barbeque here is outstanding and I am loving it. The immediate difference that I felt here, at the Department of Neurology and the Center for Neurodegeneration and Neurotherapeutics is this unparalleled platform to promote the research portfolio of junior investigators such as myself.

What passions or hobbies do you have outside of Duke?
I like to read detective novels, Bengali and English both. Al is a huge advocate of work life balance. Now that my papers are in the last lap I have started relaxing a bit more and dabbling at oil painting. I am also an organizing member of Science and Research Opportunities in India (http://sciroi.net/) which is a volunteer organization to establish collaborative research opportunities between the USA and India, and a forum which meets yearly in the University of Chicago for paving the path for return of U.S.-trained scientists of Indian origin in academic institutes and industrial bodies in India.

Dastidar enjoys a day off with his wife Ranita and son Hridhaan in Carlsbad, a flower field in San Diego.